We propose to assess in vivo and regionally metabolic pathways in various organs by following the fate of radioactively labeled metabolic substrates. The goal of this investigation is to develop and apply methods for the in vivo and regional measure of physiological processes which will be ultimately applied to the understanding of basic biological processes and to the understanding and diagnosis of pathology. Our approach consists of labeling selected metabolic substrates or other molecules of importance in physiological processes with a radioactive nuclide which emits high energy electromagnetic radiation. After the administration of the substrate to the subject under study, the location of the nuclide as a function of time is followed by externally placed detectors or a positron emission transverse tomograph (PETT), and the metabolic pathway under study is unraveled through the application of a suitable mathematical model. For this purpose, the labels used must be, with few exceptions, nuclides akin to those found in the chemical structure of living matter. We used carbon-11, nitrogen-13, oxygen-15, and, in some instances in labeling substrate analogs, fluorine-18. These nuclides are prepared by a cyclotron located in our medical center. All of them decay with the emission of positrons which, as they are absorbed, generate the annihilation radiation which is used in generating "functional images". The program is divided into four areas: (1) Chemical investigations; (2) Neurovascular studies; (3) Cardiovascular studies, and (4) Nuclear Medicine applications. The above four projects share the common core facilities, and are extensively cross-linked by the methodology used.